Immune response to Zika virus contributes to fetal harm

The same proteins that mount a potent immune response to Zika viral infection can also harm the placenta and fetal development, according to a Yale-led study.

The same proteins that mount a potent immune response to Zika viral infection can also harm the placenta and fetal development, according to a Yale-led study published in Science Immunology.

Zika researchers had established that these antiviral proteins, known as type I interferons, were required to fight Zika infection in mothers. But it was not clear what role interferons played in providing an immune defense for the fetus.

To investigate, the team led by immunobiologist Akiko Iwasaki studied two different types of mouse models. One type lacked the receptor for type 1 interferon altogether, and the other had only one copy of the interferon receptor gene. Only the latter showed signs of abnormal placental development, restricted fetal growth and death, the researchers said.

A microscopic image of Zika-infected placenta.
Image shows sections of placenta from Zika virus infected interferon-receptor-expressing mice. Blood vessels (green), nuclei (blue) and trophoblast cells (red).

The finding demonstrates that the damaging effects of the immune response to Zika virus can outweigh the benefits for fetuses, said the researchers, noting that although type 1 interferon is critical to blocking replication of the virus, too much of it can be detrimental during pregnancy. The study results may have implications for other infection-related pregnancy complications and possible interventions.

Other authors are Laura J. Yockey, Kellie A. Jurado, Nitin Arora, Alon Millet, Tasfia Rakib, Kristin M. Milano, Andrew K. Hastings, Erol Fikrig, Yong Kong, Tamas L. Horvath, Scott Weatherbee, Harvey J. Kliman, and Carolyn B. Coyne.

This study was supported in part by the National Institutes of Health.

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Ziba Kashef: ziba.kashef@yale.edu, 203-436-9317